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WO1993007874A1 - Composition medicamenteuse pour application locale - Google Patents

Composition medicamenteuse pour application locale Download PDF

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Publication number
WO1993007874A1
WO1993007874A1 PCT/GB1992/001951 GB9201951W WO9307874A1 WO 1993007874 A1 WO1993007874 A1 WO 1993007874A1 GB 9201951 W GB9201951 W GB 9201951W WO 9307874 A1 WO9307874 A1 WO 9307874A1
Authority
WO
WIPO (PCT)
Prior art keywords
composition
glycol
physiologically acceptable
skin
methotrexate
Prior art date
Application number
PCT/GB1992/001951
Other languages
English (en)
Inventor
Ian Flockhart
Ali Altunkaya
Original Assignee
Ian Flockhart
Ali Altunkaya
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Priority claimed from GB919122768A external-priority patent/GB9122768D0/en
Priority claimed from GB919122766A external-priority patent/GB9122766D0/en
Application filed by Ian Flockhart, Ali Altunkaya filed Critical Ian Flockhart
Publication of WO1993007874A1 publication Critical patent/WO1993007874A1/fr

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Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K9/00—Medicinal preparations characterised by special physical form
    • A61K9/0012—Galenical forms characterised by the site of application
    • A61K9/0014—Skin, i.e. galenical aspects of topical compositions
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
    • A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K36/00—Medicinal preparations of undetermined constitution containing material from algae, lichens, fungi or plants, or derivatives thereof, e.g. traditional herbal medicines
    • A61K36/18—Magnoliophyta (angiosperms)
    • A61K36/185—Magnoliopsida (dicotyledons)
    • A61K36/61—Myrtaceae (Myrtle family), e.g. teatree or eucalyptus
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/06—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite
    • A61K47/08—Organic compounds, e.g. natural or synthetic hydrocarbons, polyolefins, mineral oil, petrolatum or ozokerite containing oxygen, e.g. ethers, acetals, ketones, quinones, aldehydes, peroxides
    • A61K47/10—Alcohols; Phenols; Salts thereof, e.g. glycerol; Polyethylene glycols [PEG]; Poloxamers; PEG/POE alkyl ethers

Definitions

  • the present invention relates to a medicament composition, notably one containing methotrexate and its analogues, and to a method for administering the medicament topically, notably in the treatment of proliferative skin disorders e.g. psoriasis and some cutaneous malignant neoplasms.
  • a medicament composition notably one containing methotrexate and its analogues
  • a method for administering the medicament topically notably in the treatment of proliferative skin disorders e.g. psoriasis and some cutaneous malignant neoplasms.
  • Some diseases of the dermis and epidermis are characterised by cellular hyper proliferation (increased cell turnover rates), for example psoriasis.
  • Current treatment regimes range from topical corticosteroid therapy to active chemotherapy with tar and dithranol paints and baths and phototherapy involving P ⁇ VA.
  • the risks attached to the steroid regimes are those associated with the long term use of potent steroids (viz. adrenocortical suppression); whilst the latter regimes suffer from the unpleasantness attached to the treatment schedule and, with PUVA, to questions concerning long term safety and carcinogenicity.
  • Methotrexate has been used for the treatment of active psoriasis since at least 1958 (Edmundson & Guy). It is effective in controlling moderate to severe psoriasis using divided doses generally not exceeding 25mg/week, the doses being administered either orally or parenterally.
  • methotrexate as currently practised is invariably associated with long term changes in liver function and possible damage to other dividing cells, e.g. in the bone marrow and gut.
  • methotrexate In order to reduce these undesirable side effects of methotrexate, it has been proposed that it should be applied topically. However, no successful topical preparation or method of application has yet been achieved. Thus, a number of workers have reported on failures to control psoriasis with topical applications of methotrexate in a variety of formulations [see for instance Weinstein (1969), Van Scott (1959), Nurse (1963) and Cor aish (1969)]. In British Application No 2143433A it has been proposed to use the methotrexate entrapped in a liposomal formulation. However, the preparation of such an entrapped form of the medicament is complex and expensive, the composition is not effective to transfer the medicament across the skin and problems with long term stability and shelf life exist.
  • European Patent Application No 0247900A reviews much of the earlier work on the topical application of methotrexate and confirms that the earlier work had failed to find a satisfactory method for applying the medicament topically.
  • a skin penetration agent such as a l-substituted-azacycloheptan-2- one (Azone)
  • Azone l-substituted-azacycloheptan-2- one
  • the present invention provides a composition suitable for the topical application of methotrexate and its analogues, notably in the topical treatment of proliferative skin disorders, which composition comprises a therapeutic- ally effective amount of the medicament in a dermatologic ⁇ ally acceptable carrier medium, characterised in that the carrier medium comprises as essential components at least three ingredients selected from the group consisting of: a.
  • aphysiologicallyacceptablepolyalkylene-ether-glycol notably one of the empirical formula HO-(C n H 2n O) m -OH, where n has an average value of from 2 to 6 and m has an average value of from 2 to 30 or more, in which the alkylene groups can be straight or branched chain, saturated or unsaturated, and in which the hydroxyl groups can be primary, secondary and/or tertiary, and/or a physiologically acceptable polyalkylene-glycol, notably one of the empirical formula HO-(C p H 2p ) q -OH, where p_ has a value of from 2 to 6 and g has an average value of from 1 to 30, in which the alkylene groups can be straight or branched, saturated or unsaturated, and the hydroxyl groups can be primary, secondary and/or tertiary; or mixtures of such ether glycols and/or glycols; b.
  • a physiologically acceptable C 8 -C u aliphatic monohydric alcohol notably a C 9 . 12 alcohol, for example lauryl or dodecyl alcohol, which latter may be derived from propylene tetramer
  • a physiologically acceptable plant extract having anti- fungal and/or anti-bacterial properties at physiologically acceptable dosage levels, for example an essential oil, notably one containing a terpenoid compound, preferably an oxygen-containing terpene or mixture of such terpenes, for example as is present in tea tree oil and other essential oils derived from vegetable matter
  • a physiologically acceptable material having skin moisturising properties.
  • the ingredients of the composition of the invention interact synergistically to achieve a greater than expected transdermal effect and this effect is achieved when three of the specified ingredients are present in the composition.
  • the composition contains all four of the essential ingredients, optionally in admixture with other ingredients typically present in topical preparations.
  • the medicament is present in from 0.1 to 10%
  • the ether glycol and/or glycol ingredient a is present in a total amount of from 0.25 to 30%
  • the essential oil ingredient c_ is present in from 0.1 to 10%
  • the alcohol ingredient b is present in from 0.5 to 10%
  • the skin moisturiser ingredient d is present in from 0.1 to 5%, all percentages being by weight of the active ingredient based on the total composition.
  • the remainder of the composition is typically water or a water based gel or matrix having the medicament and essential ingredients uniformly distributed throughout.
  • the invention also provides a method for treating a proliferative skin disorder in a mammal, which method comprises administering a medicament transdermally by applying a biologically effective amount of a composition of the invention to the skin of the mammal, notably to or adjacent to the locus or. expected locus of the disorder.
  • the invention is applicable to methotrexate and its analogues which are effective against proliferative skin disorders.
  • the analogues of methotrexate suitable for present use include 3' ,5'-dichloromethotrexate-, and mono- and/or dialkyl esters of methotrexate or 3 ' ,5'—dichloro ⁇ methotrexate, notably those where the alkyl groups contain from 1 to 5 carbon atoms, for example the mono- or di-methyl or mono- or di-ethyl esters.
  • the invention may also be applied to precursors of the active medicaments, for example an acetate or acyl derivative, an alkali metal salt or an amine salt or complex thereof.
  • medicament will be used herein to denote in general terms methotrexate itself, its analogues and precursors thereof, whether alone or in admixture with one another.
  • composition of the invention finds widespread use in the treatment of a wide range of conditions for which the medicaments have been indicated, notably in the treatment of proliferative skin disorders for example: psoriasis; primary malignant disease, for example squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Kaposis sarcoma, etc;; and secondary deposits in the skin and neoplasms due to or associated with warts, herpes simplex, human papilloma virus etc..
  • proliferative skin disorders for example: psoriasis; primary malignant disease, for example squamous cell carcinoma, basal cell carcinoma, malignant melanoma, Kaposis sarcoma, etc; and secondary deposits in the skin and neoplasms due to or associated with warts, herpes simplex, human papilloma virus etc.
  • the skin penetration properties of formulations containing at- least three, and preferably all four, of the specified ingredients in the carrier composition are generally superior to the rates obtained with formulations which contain other ingredients, for example Azone as a penetration assistant, or formulations which do not contain at least three of the specified ingredients.
  • the invention thus offers the ability to apply methotrexate and its analogues transdermally in effective amounts and also to use lower concentrations of the medicament.
  • the compositions of the invention preferably contain from 0.01 to 2% by weight of methotrexate, which is of advantage where large areas of the skin are to be treated.
  • higher proportions for example from 5 to 10% by weight, may be used if desired and acceptable.
  • the medicament is put up in a carrier composition for application to the skin.
  • the carrier composition may contain customary ingredients used in such compositions. However, we have found that the carrier composition must contain at least three of the specified ingredients in order to obtain the enhanced penetration of the medicament through the skin.
  • the order of preference for the specified ingredients to be present is:
  • the polyalkylene ether glycols or alkylene glycols for present use as ingredient a typically have a molecular weight in the range 100 to 600,000, but are preferably those having a molecular weight in the range 200 to 6000.
  • ether ,glycols and glycols provide the carrier with occlusive properties as well as providing solvent and transdermal properties. Their inclusion in the carrier composition is especially preferred when the medicament is to be applied over a prolonged period where drying out of the skin could occur.
  • the ehter glycols and glycols also assist formation of a matrix within which the other components of the composition are dispersed to provide a stable viscous gel consistency to the composition. Where the ehter glycol or glycol has a short chain, for example 2 to 5 carbon atoms, the ether glycol or glycol may also serve as a solvent or co-solvent for other components of the composition.
  • the polyalkylene ether glycols and/or alkylene glycols are typically present in a total amount up to about 30% by weight of the total composition, preferably 1 to 25%, and mixtures of glycols and ether glycols may be used.
  • the long chain alcohol ingredient b is preferably a straight chain aliphatic alcohol containing from 9 to 12 carbon atoms, or the analogous branched chain alcohols obtained by condensation of propylene.
  • the alcohol serves as a lubrifacient to aid direct application of the composition to the skin and also assists transdermal penetration of the medicament.
  • the presence of the long chain alcohol is therefore preferred when the composition would otherwise be excessively viscous and is particularly desirable when the polyalkylene ether glycol or alkylene glycol is also present.
  • the long chain alcohol ingredient b is present in an amount of up to about 30%, for example from 1 to 25%, preferably 1 to 10%, of the total composition.
  • the plant extract ingredient c. can be selected from a wide range of such material which exhibit anti-fungal and/or anti-bacterial properties.
  • the plant extract also exhibits preservative properties at dosage rates of the ingredient which are physiologically acceptable. That is, the plant extract exhibits physiologically useful effects at a dosage rate similar to the rate at which the other ingredients are applied to the skin in the composition.
  • the amount of the plant extract required to achieve useful effects does not imbalance the overall composition.
  • the plant extract is an essential oil as defined at page 670 of Martindale, The Extra Pharmacopoeia, 28th edition.
  • essential oils include those derived from the foliage of plants and trees and are typified as containing terpenoid compounds. These may be hydrocarbon terpenes or oxygen containing compounds, for example terpene alcohols, ketones or oxides.
  • Specific preferred terpene compounds include a-pinene, a-terpinene, limonene, 1,8-cineol, gamma- terpinene, p-cymene, l-terpinen-4-ol, aromadendrene, a- terpineol, and mixtures thereof.
  • the terpene compounds for present use may be synthetic or naturally occurring, as when a eucalyptus type tree oil is used, notably the oil from Melaleuca alternifolia tree, known as Tea Tree Oil.
  • the plant extract ingredient c. may thus be used as the naturally occurring mixture of materials containing the active ingredient, or may be used in the form of an isolated and refined extract containing a raised proportion of the active ingredient or as an individual synthetically prepared single compound or mixture of isomers.
  • the plant extract ingredient c is typically present in up to
  • the skin moisturising agent for use as ingredient d is a compound or mixture of compounds which maintains or increases the hydration of the stratum corneum of the skin.
  • a number of materials are known to possess this property and specific examples include: urea; lactic, ascorbic or glycollic acids and salts thereof; cholesterol; liposomes and niosomes; pyrrolidone carboxylic acid and salts thereof; gamma-linoleic acid and its salts; mono- and poly- aminosaccharides; chitins and chemically modified chitins which contain ether and extra alkyl groups; and hyaluronic acid. Mixtures of such skin moisturising agents may be used if desired.
  • the skin moisturising agent ingredient d is present in an amount of up to about 10%, for example from 0.1 to 5%, preferably from 0.1 to 2% by weight of the total composition.
  • the composition may contain other ingredients normally present in topically applied compositions. Typically these will provide up to 50%, for example from 0.1 to 35% by weight of the total composition.
  • Such other ingredients include for example solvents or co- solvents, such as water, low molecular weight alcohols, eg. ethyl or propyl alcohols or glycols; and penetration enhancers, such as long chain acids, esters, glycols or saccharide derivatives.
  • solvents or co- solvents such as water, low molecular weight alcohols, eg. ethyl or propyl alcohols or glycols
  • penetration enhancers such as long chain acids, esters, glycols or saccharide derivatives.
  • the presence of long chain fatty acids and derivatives, notably esters, thereof is especially preferred since they aid formation of stable gels when all four of the specified ingredients are present.
  • Particularly preferred fatty acids and esters thereof for present use are those of the empirical formula Alk-OOCAcid where Alk denotes a straight or branched alkyl group containing from 2 to 18 carbon atoms and Acid denotes a saturated or unsaturated straight or branched chain alkyl group which may carry one or more Alk-OOC- substituents.
  • Typical of such fatty acid esters are C 1 to C 18 alkyl esters of octanoic acid or octanoic acid itself.
  • ingredients which may also be present include, for example, a pH controlling agent such as sodium, potassium, ammonium or an alkaline-earth metal hydroxide, or an organic base of the primary, secondary or tertiary amine type, to give a final pH in the range 4.5 - 9.0 and more preferably 7.0 - 8.5.
  • a pH controlling agent such as sodium, potassium, ammonium or an alkaline-earth metal hydroxide, or an organic base of the primary, secondary or tertiary amine type, to give a final pH in the range 4.5 - 9.0 and more preferably 7.0 - 8.5.
  • the ingredients c are often obtained from natural materials and will therefore differ in composition and be a mixture of the desired ingredient with other materials. Such mixtures may be used without the need to isolate the specified essential ingredient and the percentages given above are in terms of the desired component of such mixtures. Where the mixture contains large amounts of physiologically acceptable other components, these may themselves provide beneficial other properties, for example fragrance to the composition, and it may be necessary to use larger amounts of the mixture to achieve the desired proportion of the desired essential oil than the percentages given above. The percentages should therefore be treated as guides to the desired amounts and the optimal amounts can be readily determined by simple tests.
  • compositions of the invention can be prepared using a wide range of techniques., for example by admixing and stirring together the . desired amounts of the various ingredients to form a cream, paste or gel. If desired, the ingredients can be pre-dissolved or suspended in one or more of the other ingredients, for example in a propylene glycol solvent, to aid formation of a stable gel or emulsion. In some cases it may be desirable to subject the composition at some stage during its preparation to high speed shear working taking care to avoid entraiment of air, notably where a resin thickener or cellulose derivative is used as a gelling agent. Where necessary, the pH of the composition can be adjusted by the addition of a suitable pH regulator after the other ingredients have been incorporated.
  • compositions of the invention are applied to the affected areas of the skin of a mammal, notably a human being, to treat the psoriasis or other skin disorder by applying the composition as a coating over the affected area or can be applied to any other desired area where the medicament is to be absorbed into the body for a systemic effect elsewhere in the body.
  • This can be achieved by applying the composition directly in the required amount as a cream, paste or gel to the skin, for example by wiping a gel stick presentation of the composition which exposes the desired length of the gel stick across the desired area pf the skin until the exposed portion of the stick has been applied to the skin.
  • the composition can be put up in a pressurised dispenser formulation and applied as a spray, foam, mousse or gel via a metered dose valve, which dose can thenn be spread over and/or massaged into the skin.
  • the composition can be applied to an adhesive plaster, pad, gauze or other backing support member or carrier which is then applied over the affected area.
  • the coating of the composition on the skin or the backing support can have applied thereto a vapour barrier film, for example a plastic film or a spray on film-forming resin, for example a synthetic skin. , type composition, which serves to retain water and other fluids in the composition and the skin.
  • a vapour barrier film for example a plastic film or a spray on film-forming resin, for example a synthetic skin.
  • type composition which serves to retain water and other fluids in the composition and the skin.
  • the polyalkylene ether glycol or alkylene glycol ingredient a is present in sufficient amounts, this may provide a gel matrix for the other components and also impart sufficient occlusive properties for the use of
  • the amount of the composition of the invention applied to the skin will be sufficient to apply the biologically effective amount of the medicament. This amount will vary according to the treatment required and the content of active ingredient in the composition. The optimal amount of the composition to be applied can be readily established as is known from a knowledge of these.
  • a co-solution of stearic acid (8 parts by weight) and propylene glycol (8 parts by weight) was prepared at 70°C with, mechanical stirring.
  • a separate solution of a mixture of polyethylene glycol (ingredient a, average molecular weight 400, 6 parts by weight) in polyethyene glycol (ingredient a, average molecular weight 4000, 20 parts by weight) was prepared similarly.
  • the two solutions were mixed together at 60-65°C using a mixer without entrainment of air.
  • a solution of sodium hydroxide (1.12 parts), a polyaminosaccharide condensate skin moisturising agent (ingredient d, 1.1 parts., by weight) in deionised water (25 parts by volume) was slowly added with stirring.
  • the mixture was slowly cooled to 30°C with high shear mixing without entrainment of air to give a visous white pastey mass.
  • the mass was mixed with a solution of Tea Tree oil (ingredient c, l part by volume), dodecanol (ingredient b, 2 parts by weight) and, as a lubrifacient to aid preparaton of the mixture and application of the composition to the skin, an emollient ester of polypropylene glycol and myristic acid (0.2 parts by weight) in ethanol (24 parts by volume) .
  • the mixture was stirred continuously for one hour to give a creamy hydrogel base and packed into a sealed container until used (Formulation II, FII). Similar hydrogel base compositions were made but with varying ingredients as set out below:
  • Formulation I FII, dodecanol ingredient b omitted
  • Formulation III FII
  • cetyl alcohol replaces dodecanol
  • Formulation IV FII, moisturising agent ingredient d omitted
  • Formulation V FII, methyl cellulose (5 parts) in place of polyethylene glycol ingredient a
  • Formulation VI FII, emollient and moisturising agent ingredients . d replaced with a saccharide ester emollient
  • Formulation VII FII, omitting the essential oil ingredient c .
  • Methotrexate of BP grade was mechanically admixed in varying amounts (1% w/w, 0.5% w/w, 0.25% w/w, 0.2% w/w and 0.1% w/w) with the hydrogel bases and the resultant compositions stored in sealed, light-tight containers until used.
  • compositions were applied as a coating of 0.05 to 0.1 grams per square cm to samples of isolated human stratum corneum (obtained from mammary reduction or abdomenoplasty for several different donors) prepared as described by Skerrow & Skerrow (1985) or Kligman & Christophers (Arch.Der atol. 88.702 (1974).
  • Transdermal delivery was measured in micrograms per square centimetre per hour using a stability indicating hplc assay method, sampling the stirred receptor layer over periods up to 96 hours.
  • the cells made of glass
  • the compositions ' were applied to the epidermal surface of the stratum corneum and the dermal side was bathed by a stirred phosphate buffered saline solution containing 10% ethanol. The system was maintained at 32 degrees, light was excluded and the exposed surface of the applied composition was occluded to prevent alcohol and water loss. Two or more cells were run for each formulation and the skin integrity was assessed visually both before and after the experiment using a hand lens.
  • Formulation Ila formulation II with addition of 1 part of a silicone wetting agent - dimethicone CS20.

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Abstract

La présente invention se rapporte à une composition destinée à être appliquée localement sur la peau d'une personne. Cette composition comprend un méthotrexate ou analogue de celui-ci dans un milieu porteur dermatologiquement acceptable, caractérisée en ce qu'il comporte comme constituants essentiels au moins trois ingrédients, sélectionnés dans le groupe constitué par: a) un polyalkylène éther-glycol ou un alkylène-glycol physiologiquement acceptable, ou des mélanges de ces éthers glycols et/ou glycols; b) un alcool aliphatique C8-C14 monohydrique physiologiquement acceptable; c) un extrait de plante physiologiquement acceptable possédant des propriétés antifongiques et/ou anti-bactéries à des niveaux de dosages physiologiquement acceptables; et d) une matière physiologiquement acceptable possédant des propriétés hydratantes pour la peau. L'invention se rapporte également à l'application transdermique d'un méthotrexate ou analogue de celui-ci qui consiste à appliquer une quantité biologiquement efficace d'une composition de l'invention sur la peau.
PCT/GB1992/001951 1991-10-26 1992-10-23 Composition medicamenteuse pour application locale WO1993007874A1 (fr)

Applications Claiming Priority (4)

Application Number Priority Date Filing Date Title
GB919122768A GB9122768D0 (en) 1991-10-26 1991-10-26 Medicament composition
GB9122766.0 1991-10-26
GB9122768.6 1991-10-26
GB919122766A GB9122766D0 (en) 1991-10-26 1991-10-26 Medicament composition

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WO1993007874A1 true WO1993007874A1 (fr) 1993-04-29

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PCT/GB1992/001951 WO1993007874A1 (fr) 1991-10-26 1992-10-23 Composition medicamenteuse pour application locale

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AU (1) AU2808492A (fr)
MX (1) MX9206158A (fr)
WO (1) WO1993007874A1 (fr)

Cited By (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5738863A (en) * 1994-04-12 1998-04-14 Sackin; Bradley M. Honey bee repellent composition comprising tea tree oil
US5958420A (en) * 1997-03-13 1999-09-28 Nortrade Medical, Inc. Treatment of burns, cuts, and abrasions of the skin
US6485740B1 (en) * 2000-03-14 2002-11-26 Yutoku Pharmaceutical Ind., Co., Ltd. Transdermal methotrexate preparations
KR100439204B1 (ko) * 2000-10-25 2004-07-07 주식회사 삼양사 메토트렉세이트를 유효성분으로 함유하는 경피투여용 조성물
EP1809291A1 (fr) * 2004-11-03 2007-07-25 Forhumantech. Co., Ltd. Compositions pharmaceutiques destinees a etre administrees par voie transdermique
US9968800B2 (en) 2016-02-09 2018-05-15 Luma Therapeutics, Inc. Methods, compositions and apparatuses for treating psoriasis by phototherapy
US10058711B2 (en) 2014-02-26 2018-08-28 Luma Therapeutics, Inc. Phototherapy dressing for treating psoriasis

Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB496893A (en) * 1937-06-08 1938-12-08 Robert Edwin Goldsbrough Vegetable oil preparations for external application to the body
GB1001949A (en) * 1961-07-20 1965-08-18 Friedrich Meyer Penetrating agents
EP0069385A2 (fr) * 1981-07-07 1983-01-12 Merck & Co. Inc. Emploi de l'eucalyptol pour favoriser la pénétration à travers la peau de substances biologiquement actives
GB2143433A (en) * 1983-06-20 1985-02-13 Hariprasad Manibhai Patel Methotrexate ointment
EP0247900A1 (fr) * 1986-05-30 1987-12-02 The Regents Of The University Of California Préparation topique de méthotrexate pour le traitement de maladies hyperprolifératives épithéliales
US4797402A (en) * 1987-06-02 1989-01-10 Dorsey Kenneth E Cooling anti-itch skin preparations

Patent Citations (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
GB496893A (en) * 1937-06-08 1938-12-08 Robert Edwin Goldsbrough Vegetable oil preparations for external application to the body
GB1001949A (en) * 1961-07-20 1965-08-18 Friedrich Meyer Penetrating agents
EP0069385A2 (fr) * 1981-07-07 1983-01-12 Merck & Co. Inc. Emploi de l'eucalyptol pour favoriser la pénétration à travers la peau de substances biologiquement actives
GB2143433A (en) * 1983-06-20 1985-02-13 Hariprasad Manibhai Patel Methotrexate ointment
EP0247900A1 (fr) * 1986-05-30 1987-12-02 The Regents Of The University Of California Préparation topique de méthotrexate pour le traitement de maladies hyperprolifératives épithéliales
US4797402A (en) * 1987-06-02 1989-01-10 Dorsey Kenneth E Cooling anti-itch skin preparations

Cited By (8)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US5738863A (en) * 1994-04-12 1998-04-14 Sackin; Bradley M. Honey bee repellent composition comprising tea tree oil
US5958420A (en) * 1997-03-13 1999-09-28 Nortrade Medical, Inc. Treatment of burns, cuts, and abrasions of the skin
US6485740B1 (en) * 2000-03-14 2002-11-26 Yutoku Pharmaceutical Ind., Co., Ltd. Transdermal methotrexate preparations
KR100439204B1 (ko) * 2000-10-25 2004-07-07 주식회사 삼양사 메토트렉세이트를 유효성분으로 함유하는 경피투여용 조성물
EP1809291A1 (fr) * 2004-11-03 2007-07-25 Forhumantech. Co., Ltd. Compositions pharmaceutiques destinees a etre administrees par voie transdermique
EP1809291A4 (fr) * 2004-11-03 2012-04-04 Forhumantech Co Ltd Compositions pharmaceutiques destinees a etre administrees par voie transdermique
US10058711B2 (en) 2014-02-26 2018-08-28 Luma Therapeutics, Inc. Phototherapy dressing for treating psoriasis
US9968800B2 (en) 2016-02-09 2018-05-15 Luma Therapeutics, Inc. Methods, compositions and apparatuses for treating psoriasis by phototherapy

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MX9206158A (es) 1993-08-01

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